Various discussions have been made on the production of nucleic acid derivatives. It is general to use a process wherein a base and a sugar are condensed with the use of a Lewis acid catalyst, in particular, the process wherein SnCl4 or trimethylsilyl trifluoromethanesulfonate is used as the Lewis acid catalyst.
As an example of such process with the use of a uracil derivative as the base, it is known to condense acylated ribose with azauracil (J. Org. Chem., Vol. 39, p. 3654-3663 (1974)). From the viewpoint of industrial production, however, this process has some problems such that SnCl4 and ZnCl2 which are regarded as favorable Lewis acid catalysts are expensive reagents and attention should be paid to the removal of the residues of these catalysts containing heavy metals such as Sn and Zn in case of producing intermediates for pharmaceuticals.
Moreover, Published Chinese Patent Application No. 1216766 discloses condensation of 1,2,3,5-tetra-O-acetyl-β-ribofuranose with 5-methyluracil and it is generally described that various Lewis acids are usable therefore. However, only SnCl4 was employed and this process suffers from the same problems in the industrial production.
As examples with the use of a triazole derivative as a base, there are known processes reported in Chem. Ber., vol. 114, p. 1234-1255 (1981), Revue Roumaine de Chimie, vol. 32, p. 329-333 (1987) and Nucl. Acid. Chem., vol. 1, p. 255-260 (1978). In each of these cases, use is exclusively made of trimethylsilyl trifluoromethanesulfonate, trimethylsilane iodide or mercury chloride as the Lewis acid.
In case of condensing sugar as intermediates for pharmaceuticals or agricultural chemicals, stereoselective production is carried out. In such a process, it is preferable from an industrial viewpoint to re-use stereoisomers other than the desired one. In case of condensing a nucleic acid derivative, a β-anomer is most frequently employed. Thus, it is industrially favorable that a β-anomer can be conveniently obtained by isomerizing the undesired α-anomer, if possible. Moreover, it is difficult to obtain starting materials of sugars having 1,2-cis configuration. Therefore, it has been required to establish a method of industrially effectively obtain these materials from stereoisomers thereof which can be more easily obtained.
As a process for isomerizing (epimerizing) a stereoconfiguration on the carbon atom at the 1-position of a sugar, there has been known only one process whereby pentaacetyl-β-mannose which is a 6-membered sugar is isomerized in the presence of acetic anhydride and zinc chloride (J. Am. Chem. Soc., 40, 992 (1918)). In this process, zinc chloride which is a Lewis acid is used as a catalyst in the reaction. Thus, there arise some problems such that the reagent is poor in handling properties due to its high hygroscopicity and troublesome procedures are needed in the isolation and purification after the completion of the reaction. Namely, this process is not favorable from an industrial viewpoint.